Proceedings of the National Academy of Sciences - PNAS, 2012-02, Vol.109 (9), p.3528-3533
2012
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- Autor(en) / Beteiligte
- Titel
- Ganglioside GM1 induces phosphorylation of mutant huntingtin and restores normal motor behavior in Huntington disease mice
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 2012-02, Vol.109 (9), p.3528-3533
- Ort / Verlag
- United States: National Academy of Sciences
- Erscheinungsjahr
- 2012
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Huntington disease (HD) is a progressive neurodegenerative monogenic disorder caused by expansion of a polyglutamine stretch in the huntingtin (Htt) protein. Mutant huntingtin triggers neural dysfunction and death, mainly in the corpus striatum and cerebral cortex, resulting in pathognomonic motor symptoms, as well as cognitive and psychiatric decline. Currently, there is no effective treatment for HD. We report that intraventricular infusion of ganglioside GM1 induces phosphorylation of mutant huntingtin at specific serine amino acid residues that attenuate huntingtin toxicity, and restores normal motor function in already symptomatic HD mice. Thus, our studies have identified a potential therapy for HD that targets a posttranslational modification of mutant huntingtin with critical effects on disease pathogenesis.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424eISSN: 1091-6490DOI: 10.1073/pnas.1114502109Titel-ID: cdi_proquest_journals_926555839
- Format
- –
- Schlagworte
- Amino acids, Animals, Antibodies, Biological Sciences, cerebral cortex, Codon - drug effects, cognition, Cognitive ability, Corpus striatum, Corpus Striatum - metabolism, Cortex, death, Dimerization, Disease Models, Animal, Dopamine and cAMP-Regulated Phosphoprotein 32 - biosynthesis, Dopamine and cAMP-Regulated Phosphoprotein 32 - genetics, Drug Evaluation, Preclinical, G(M1) Ganglioside - administration & dosage, G(M1) Ganglioside - therapeutic use, Ganglioside GM1, Gangliosides, Huntingtin, Huntingtin Protein, Huntington disease, Huntington's disease, Huntingtons disease, Infusion Pumps, Implantable, Infusions, Parenteral, Medical treatment, Mice, Mice, Neurologic Mutants, Motor ability, Motor Activity - drug effects, mutants, Mutation, Nerve Tissue Proteins - biosynthesis, Nerve Tissue Proteins - genetics, Nerve Tissue Proteins - metabolism, Nervous system diseases, Neurological disorders, Neurons, Neurons - metabolism, Neuroscience, Nuclear Proteins - metabolism, pathogenesis, Phosphorylation, Phosphorylation - drug effects, Phosphoserine - analysis, Polyglutamine, post-translational modification, Protein Processing, Post-Translational - drug effects, Psychomotor Performance - drug effects, Serine, therapeutics, Toxicity